5UH8

Crystal structure of Mycobacterium tuberculosis transcription initiation complex containing 4nt RNA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.18 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.204 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition.

Lin, W.Mandal, S.Degen, D.Liu, Y.Ebright, Y.W.Li, S.Feng, Y.Zhang, Y.Mandal, S.Jiang, Y.Liu, S.Gigliotti, M.Talaue, M.Connell, N.Das, K.Arnold, E.Ebright, R.H.

(2017) Mol Cell 66: 169-179.e8

  • DOI: https://doi.org/10.1016/j.molcel.2017.03.001
  • Primary Citation of Related Structures:  
    5UH5, 5UH6, 5UH7, 5UH8, 5UH9, 5UHA, 5UHB, 5UHC, 5UHD, 5UHE, 5UHF, 5UHG

  • PubMed Abstract: 

    Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. Mtb RNA polymerase (RNAP) is the target of the first-line antituberculosis drug rifampin (Rif). We report crystal structures of Mtb RNAP, alone and in complex with Rif, at 3.8-4.4 Å resolution. The results identify an Mtb-specific structural module of Mtb RNAP and establish that Rif functions by a steric-occlusion mechanism that prevents extension of RNA. We also report non-Rif-related compounds-Nα-aroyl-N-aryl-phenylalaninamides (AAPs)-that potently and selectively inhibit Mtb RNAP and Mtb growth, and we report crystal structures of Mtb RNAP in complex with AAPs. AAPs bind to a different site on Mtb RNAP than Rif, exhibit no cross-resistance with Rif, function additively when co-administered with Rif, and suppress resistance emergence when co-administered with Rif.


  • Organizational Affiliation

    Waksman Institute and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase subunit alpha
A, B
347Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: rpoARv3457cMTCY13E12.10c
EC: 2.7.7.6
UniProt
Find proteins for P9WGZ1 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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Go to UniProtKB:  P9WGZ1
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UniProt GroupP9WGZ1
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase subunit beta1,178Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: rpoBRv0667MTCI376.08c
EC: 2.7.7.6
UniProt
Find proteins for P9WGY9 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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UniProt GroupP9WGY9
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase subunit beta'1,316Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: rpoCLH57_03610
EC: 2.7.7.6
UniProt
Find proteins for P9WGY7 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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UniProt GroupP9WGY7
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-directed RNA polymerase subunit omega110Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: rpoZRv1390MTCY21B4.07
EC: 2.7.7.6
UniProt
Find proteins for P9WGY5 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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UniProt GroupP9WGY5
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
RNA polymerase sigma factor SigA528Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: sigAmysArpoDrpoVRv2703MTCY05A6.24
UniProt
Find proteins for P9WGI1 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
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UniProt GroupP9WGI1
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Entity ID: 6
MoleculeChains LengthOrganismImage
DNA (5'-D(*TP*AP*TP*AP*AP*TP*GP*GP*GP*AP*GP*CP*TP*GP*TP*CP*AP*CP*GP*GP*AP*TP*G)-3')G [auth H]23Mycobacterium tuberculosis H37Rv
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Entity ID: 7
MoleculeChains LengthOrganismImage
DNA (5'-D(*CP*AP*TP*CP*CP*GP*TP*GP*AP*GP*TP*CP*GP*AP*GP*G)-3')H [auth G]16Mycobacterium tuberculosis H37Rv
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Entity ID: 8
MoleculeChains LengthOrganismImage
RNA (5'-R(*UP*CP*GP*A)-3')4Mycobacterium tuberculosis H37Rv
Sequence Annotations
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Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.18 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.204 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 151.995α = 90
b = 163.666β = 90
c = 197.782γ = 90
Software Package:
Software NamePurpose
HKL-2000data scaling
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHENIXphasing
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-04-12
    Type: Initial release
  • Version 1.1: 2017-04-26
    Changes: Database references
  • Version 1.2: 2017-05-03
    Changes: Database references
  • Version 1.3: 2017-11-22
    Changes: Refinement description